ArticleMalaria journal2014
Humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice sustain the complex vertebrate life cycle of Plasmodium falciparum malaria.
Article in Malaria journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.Antimicrobial agents and chemotherapy · 2016Trial
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.Frontiers in immunology · 2026Article
- Humanized DRAGA mice are a valuable model to study novel immunotherapies for HIV-1.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Understanding erythroid physiology and pathology in humanized mice: A closer look.British journal of haematology · 2025Review
- Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.Frontiers in cellular and infection microbiology · 2024Article
- Oleuropein mediated autophagy begets antimalarial drug resistance.Frontiers in microbiology · 2024Article
- Using CryopreservedMicroorganisms · 2023Article
- Prevalence of Malaria Parasite among Pregnant Women Attending to Saudi Kassala Teaching Hospital in Kassala State, Eastern Sudan.Journal of tropical medicine · 2023Article
- Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19.Human vaccines & immunotherapeutics · 2022Article
- In vitro models for human malaria: targeting the liver stage.Trends in parasitology · 2022Review
- Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021Review
- The humanized DRAGA mouse (HLA-A2. HLA-DR4. RAG1 KO. IL-2R g c KO. NOD) establishes inducible and transmissible models for influenza type A infections.Human vaccines & immunotherapeutics · 2020Article
- Review
- Current Challenges in the Identification of Pre-Erythrocytic Malaria Vaccine Candidate Antigens.Frontiers in immunology · 2020Review
- Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity.Malaria journal · 2018Article
- Advancing Research Models and Technologies to Overcome Biological Barriers to Plasmodium vivax Control.Trends in parasitology · 2018Review
- Generation and testing anti-influenza human monoclonal antibodies in a new humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD).Human vaccines & immunotherapeutics · 2018Article
- Article
- Engineered Livers for Infectious Diseases.Cellular and molecular gastroenterology and hepatology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalaria is a deadly infectious disease affecting millions of people in tropical and sub-tropical countries. Among the five species of Plasmodium parasites that infect humans, Plasmodium falciparum accounts for the highest morbidity and mortality associated with malaria. Since humans are the only natural hosts for P. falciparum, the lack of convenient animal models has hindered the understanding of disease pathogenesis and prompted the need of testing anti-malarial drugs and vaccines directly in human trials. Humanized mice hosting human cells represent new pre-clinical models for infectious diseases that affect only humans. In this study, the ability of human-immune-system humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice to sustain infection with P. falciparum was explored.
methodsFour week-old DRAG mice were infused with HLA-matched human haematopoietic stem cells (HSC) and examined for reconstitution of human liver cells and erythrocytes. Upon challenge with infectious P. falciparum sporozoites (NF54 strain) humanized DRAG mice were examined for liver stage infection, blood stage infection, and transmission to Anopheles stephensi mosquitoes.
resultsHumanized DRAG mice reconstituted human hepatocytes, Kupffer cells, liver endothelial cells, and erythrocytes. Upon intravenous challenge with P. falciparum sporozoites, DRAG mice sustained liver to blood stage infection (average 3-5 parasites/microlitre blood) and allowed transmission to An. stephensi mosquitoes. Infected DRAG mice elicited antibody and cellular responses to the blood stage parasites and self-cured the infection by day 45 post-challenge.
conclusionsDRAG mice represent the first human-immune-system humanized mouse model that sustains the complex vertebrate life cycle of P. falciparum without the need of exogenous injection of human hepatocytes/erythrocytes or P. falciparum parasite adaptation. The ability of DRAG mice to elicit specific human immune responses to P. falciparum parasites may help deciphering immune correlates of protection and to identify protective malaria antigens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.